LIN-28 balances longevity and germline stem cell number in Caenorhabditis elegans through let-7/AKT/DAF-16 axis.
LIN-28 balances longevity and germline stem cell number in Caenorhabditis elegans through let-7/AKT/DAF-16 axis.
复制标题
LIN-28 通过 let-7/AKT/DAF-16 轴平衡秀丽隐杆线虫的寿命和生殖干细胞数量。
DOI：
10.1111/acel.12539
复制
发表时间：
2017-02
期刊：
影响因子：
7.8
通讯作者：
Han JJ
中科院分区：
文献类型：
--
作者：
Wang D;Hou L;Nakamura S;Su M;Li F;Chen W;Yan Y;Green CD;Chen D;Zhang H;Antebi A;Han JJ
RNA结合蛋白LIN-28首次被发现控制秀丽线虫的发育时间。后来，人们发现它在哺乳动物的多能性、新陈代谢和癌症中发挥着重要作用。在这里，我们报告了低剂量的LIN-28提高了线虫的应激耐受性和寿命，并减少了线虫生殖系干细胞/祖细胞的数量。胚系LIN-28调控的microRNA let-7通过靶向AKT-1/2并降低其蛋白质水平而发挥这些作用。AKT-1/2和下游的DAF-16转录因子都是LIN-28的寿命和生殖系干细胞效应所必需的。该途径还介导了饮食限制导致生殖系干细胞数量的延长和减少。因此，我们在这里描绘的LIN-28/LET-7/AKT/DAF-16轴是一个在平衡生殖和躯体维持以及它们对环境能量水平的反应方面发挥重要作用的程序--这是调节衰老的资源分配的进化优化的中心教条。
The RNA‐binding protein LIN‐28 was first found to control developmental timing in Caenorhabditis elegans. Later, it was found to play important roles in pluripotency, metabolism, and cancer in mammals. Here we report that a low dosage of lin‐28 enhanced stress tolerance and longevity, and reduced germline stem/progenitor cell number in C. elegans. The germline LIN‐28‐regulated microRNA let‐7 was required for these effects by targeting akt‐1/2 and decreasing their protein levels. AKT‐1/2 and the downstream DAF‐16 transcription factor were both required for the lifespan and germline stem cell effects of lin‐28. The pathway also mediated dietary restriction induced lifespan extension and reduction in germline stem cell number. Thus, the LIN‐28/let‐7/AKT/DAF‐16 axis we delineated here is a program that plays an important role in balancing reproduction and somatic maintenance and their response to the environmental energy level—a central dogma of the ‘evolutionary optimization’ of resource allocation that modulates aging.